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Research progress of brain magnetic resonance imaging in patients with primary open-angle glaucoma
YANG Bingbing  QU Xiaoxia  WANG Qian  LI Ting  XIAN Junfang 

Cite this article as: Yang BB, Qu XX, Wang Q, et al. Research progress of brain magnetic resonance imaging in patients with primary open-angle glaucoma[J]. Chin J Magn Reson Imaging, 2022, 13(11): 37-41. DOI:10.12015/issn.1674-8034.2022.11.007.

[Abstract] Glaucoma is the most frequent cause of irreversible blindness worldwide. As the most prevalent type of glaucoma, primary open-angle glaucoma (POAG) is facing challenges in pathogenesis, diagnosis, and management. In recent years, neuroimaging studies including multimodal MRI have shown that POAG is considered as a neurodegenerative disease. Alterations of brain structure, function, blood perfusion, and metabolism involving visual pathway and other brain regions were shown, which were correlated with the severity of the disease in POAG patients. In the future, multi-center prospective cohort studies with large sample sizes will be more needed, and multi-modal MRI data will be analyzed with machine learning and deep learning methods to investigate the relationship between changes in the central nervous system and their correlation with retinal changes and visual disorders, to provide a more explicit basis for early diagnosis and treatment. Therefore, MRI findings of the brain in patients with POAG and the potential role in the pathogenesis and diagnosis of POAG, as well as probable solutions to the unsolved problems, were systematically reviewed, aiming to provide a reference for the researchers in this field.
[Keywords] primary open-angle glaucoma;brain;magnetic resonance imaging;multimodality;advance

YANG Bingbing   QU Xiaoxia   WANG Qian   LI Ting   XIAN Junfang*  

Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Xian JF, E-mail:

Conflicts of interest   None.

ACKNOWLEDGMENTS National Natural Science Foundation of China (No. 81571649, 81701666, 81871340, 81901719, 82071906); Special Fund for "Peak Climbing" Plan of Beijing Hospital Management Center (No. DFL20190203); Special Fund for Clinical Medicine Development of Beijing Hospital Administration (No. ZYLX201704).
Received  2022-08-08
Accepted  2022-11-10
DOI: 10.12015/issn.1674-8034.2022.11.007
Cite this article as: Yang BB, Qu XX, Wang Q, et al. Research progress of brain magnetic resonance imaging in patients with primary open-angle glaucoma[J]. Chin J Magn Reson Imaging, 2022, 13(11): 37-41. DOI:10.12015/issn.1674-8034.2022.11.007.

Jonas JB, Aung T, Bourne RR, et al. Glaucoma[J]. Lancet, 2017, 390(10108): 2183-2193. DOI: 10.1016/s0140-6736(17)31469-1.
Stein JD, Khawaja AP, Weizer JS. Glaucoma in adults-screening, diagnosis, and management: a review[J]. JAMA, 2021, 325(2): 164-174. DOI: 10.1001/jama.2020.21899.
Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis[J]. Ophthalmology, 2014, 121(11): 2081-2090. DOI: 10.1016/j.ophtha.2014.05.013.
Juźwik CA, Drake S S, Zhang Y, et al. microRNA dysregulation in neurodegenerative diseases: a systematic review[J/OL]. Prog Neurobiol, 2019, 182: 101664 [2022-03-20]. DOI: 10.1016/j.pneurobio.2019.101664.
Faiq MA, Wollstein G, Schuman JS, et al. Cholinergic nervous system and glaucoma: from basic science to clinical applications[J/OL]. Prog Retin Eye Res, 2019, 72: 100767 [2022-03-21]. DOI: 10.1016/j.preteyeres.2019.06.003.
Liu W, Ha Y, Xia F, et al. Neuronal Epac1 mediates retinal neurodegeneration in mouse models of ocular hypertension[J/OL]. J Exp Med, 2020, 217(4): e20190930 [2022-03-20]. DOI: 10.1084/jem.20190930.
De Moraes CG. Natural history of normal-tension glaucoma with (very) low intraocular pressure[J]. Ophthalmology, 2019, 126(8): 1117-1118. DOI: 10.1016/j.ophtha.2019.02.003.
Wang NL, Xie XB, Yang DY, et al. Orbital cerebrospinal fluid space in glaucoma: the Beijing intracranial and intraocular pressure (iCOP) study[J]. Ophthalmology, 2012, 119(10): 2065-2073. DOI: 10.1016/j.ophtha.2012.03.054.
Furuyoshi N, Furuyoshi M, May CA, et al. Vascular and glial changes in the retrolaminar optic nerve in glaucomatous monkey eyes[J]. Ophthalmologica, 2000, 214(1): 24-32. DOI: 10.1159/000027470.
Mendoza M, Shotbolt M, Faiq MA, et al. Advanced diffusion MRI of the visual system in glaucoma: from experimental animal models to humans[J/OL]. Biology, 2022, 11(3): 454 [2022-03-20]. DOI: 10.3390/biology11030454.
Frezzotti P, Giorgio A, Toto F, et al. Early changes of brain connectivity in primary open angle glaucoma[J]. Hum Brain Mapp, 2016, 37(12): 4581-4596. DOI: 10.1002/hbm.23330.
Wang Q, Qu XX, Chen WW, et al. Altered coupling of cerebral blood flow and functional connectivity strength in visual and higher order cognitive cortices in primary open angle glaucoma[J]. J Cereb Blood Flow Metab, 2021, 41(4): 901-913. DOI: 10.1177/0271678X20935274.
Guo LY, Wang R, Tang ZH, et al. Metabolic alterations within the primary visual cortex in early open-angle glaucoma patients: a proton magnetic resonance spectroscopy study[J]. J Glaucoma, 2018, 27(12): 1046-1051. DOI: 10.1097/IJG.0000000000001098.
Mutlu U, Colijn JM, Ikram MA, et al. Association of retinal neurodegeneration on optical coherence tomography with dementia: a population-based study[J]. JAMA Neurol, 2018, 75(10): 1256-1263. DOI: 10.1001/jamaneurol.2018.1563.
Martucci A, Picchi E, Di Giuliano F, et al. Imaging biomarkers for Alzheimer's disease and glaucoma: current and future practices[J]. Curr Opin Pharmacol, 2022, 62: 137-144. DOI: 10.1016/j.coph.2021.12.003.
Hanafiah M, Johari B, Ab Mumin N, et al. MRI findings suggestive of Alzheimer's disease in patients with primary open angle glaucoma-a single sequence analysis using rapid 3D T1 spoiled gradient echo[J/OL]. Br J Radiol, 2022, 95(1133): 20210857 [2022-03-20]. DOI: 10.1259/bjr.20210857.
Pardue MT, Allen RS. Neuroprotective strategies for retinal disease[J]. Prog Retin Eye Res, 2018, 65: 50-76. DOI: 10.1016/j.preteyeres.2018.02.002.
van der Merwe Y, Murphy MC, Sims JR, et al. Citicoline modulates glaucomatous neurodegeneration through intraocular pressure-independent control[J]. Neurotherapeutics, 2021, 18(2): 1339-1359. DOI: 10.1007/s13311-021-01033-6.
Shalaby WS, Ahmed OM, Waisbourd M, et al. A review of potential novel glaucoma therapeutic options independent of intraocular pressure[J]. Surv Ophthalmol, 2022, 67(4): 1062-1080. DOI: 10.1016/j.survophthal.2021.12.003.
Sims JR, Chen AM, Sun Z, et al. Role of structural, metabolic, and functional MRI in monitoring visual system impairment and recovery[J]. J Magn Reson Imaging, 2021, 54(6): 1706-1729. DOI: 10.1002/jmri.27367.
Beykin G, Norcia AM, Srinivasan VJ, et al. Discovery and clinical translation of novel glaucoma biomarkers[J/OL]. Prog Retin Eye Res, 2021, 80: 100875 [2022-03-20]. DOI: 10.1016/j.preteyeres.2020.100875.
Hernowo AT, Boucard CC, Jansonius NM, et al. Automated morphometry of the visual pathway in primary open-angle glaucoma[J]. Invest Ophthalmol Vis Sci, 2011, 52(5): 2758-2766. DOI: 10.1167/iovs.10-5682.
Pankowska A, Matwiejczuk S, Kozioł P, et al. Visual tract degradation in bilateral normal-tension glaucoma-cortical thickness maps and volumetric study of visual pathway areas[J/OL]. J Clin Med, 2022, 11(7): 1907 [2022-03-24]. DOI: 10.3390/jcm11071907.
Kosior-Jarecka E, Pankowska A, Polit P, et al. Volume of lateral geniculate nucleus in patients with glaucoma in 7 tesla MRI[J/OL]. J Clin Med, 2020, 9(8): 2382 [2022-03-20]. DOI: 10.3390/jcm9082382.
Giorgio A, Zhang J, Costantino F, et al. Diffuse brain damage in normal tension glaucoma[J]. Hum Brain Mapp, 2018, 39(1): 532-541. DOI: 10.1002/hbm.23862.
Gracitelli CPB, Duque-Chica GL, Sanches LG, et al. Structural analysis of glaucoma brain and its association with ocular parameters[J]. J Glaucoma, 2020, 29(5): 393-400. DOI: 10.1097/IJG.0000000000001470.
Jiang MM, Zhou Q, Liu XY, et al. Structural and functional brain changes in early- and mid-stage primary open-angle glaucoma using voxel-based morphometry and functional magnetic resonance imaging[J/OL]. Medicine, 2017, 96(9): e6139 [2022-03-20]. DOI: 10.1097/MD.0000000000006139.
Wang Y, Wang X, Zhou J, et al. Brain morphological alterations of cerebral cortex and subcortical nuclei in high-tension glaucoma brain and its associations with intraocular pressure[J]. Neuroradiology, 2020, 62(4): 495-502. DOI: 10.1007/s00234-019-02347-1.
Sidek S, Ramli N, Rahmat K, et al. Glaucoma severity affects diffusion tensor imaging (DTI) parameters of the optic nerve and optic radiation[J]. Eur J Radiol, 2014, 83(8): 1437-1441. DOI: 10.1016/j.ejrad.2014.05.014.
Wang CJ, Wang YT, Zhai FB, et al. The study of different kinds of primary glaucoma by diffusion tensor imaging[J]. Chin J Magn Reson Imaging, 2022, 13(1): 114-117. DOI: 10.12015/issn.1674-8034.2022.01.023.
Dai H, Yin DZ, Hu CH, et al. Whole-brain voxel-based analysis of diffusion tensor MRI parameters in patients with primary open angle glaucoma and correlation with clinical glaucoma stage[J]. Neuroradiology, 2013, 55(2): 233-243. DOI: 10.1007/s00234-012-1122-9.
Tellouck L, Durieux M, Coupé P, et al. Optic radiations microstructural changes in glaucoma and association with severity: a study using 3 tesla-magnetic resonance diffusion tensor imaging[J]. Invest Ophthalmol Vis Sci, 2016, 57(15): 6539-6547. DOI: 10.1167/iovs.16-19838.
Li T, Miao W, He HG, et al. Study of optic radiations in patients with primary open-angle glaucoma with diffusion tensor imaging[J]. Natl Med J China, 2017(5): 347-352. DOI: 10.3760/cma.j.issn.0376-2491.2017.05.006.
Qu XX, Wang Q, Chen WW, et al. Combined machine learning and diffusion tensor imaging reveals altered anatomic fiber connectivity of the brain in primary open-angle glaucoma[J]. Brain Res, 2019, 1718: 83-90. DOI: 10.1016/j.brainres.2019.05.006.
Xu ZF, Sun JS, Zhang XH, et al. Microstructural visual pathway abnormalities in patients with primary glaucoma: 3 T diffusion kurtosis imaging study[J/OL]. Clin Radiol, 2018, 73(6): 591.e9-e15 [2022-03-20]. DOI: 10.1016/j.crad.2018.01.010.
Nucci C, Garaci F, Altobelli S, et al. Diffusional kurtosis imaging of white matter degeneration in glaucoma[J/OL]. J Clin Med, 2020, 9(10): 3122 [2022-03-20]. DOI: 10.3390/jcm9103122.
Li T, Qu XX, Chen WW, et al. Altered information flow and microstructure abnormalities of visual cortex in normal-tension glaucoma: evidence from resting-state fMRI and DKI[J/OL]. Brain Res, 2020, 1741: 146874 [2022-03-20]. DOI: 10.1016/j.brainres.2020.146874.
Di Ciò F, Garaci F, Minosse S, et al. Reorganization of the structural connectome in primary open angle glaucoma[J/OL]. Neuroimage Clin, 2020, 28: 102419 [2022-03-20]. DOI: 10.1016/j.nicl.2020.102419.
McDowell CM, Kizhatil K, Elliott MH, et al. Consensus recommendation for mouse models of ocular hypertension to study aqueous humor outflow and its mechanisms[J/OL]. Invest Ophthalmol Vis Sci, 2022, 63(2): 12 [2022-03-24]. DOI: 10.1167/iovs.63.2.12.
Gong ZB, Chen HH, Liu SF, et al. Research progress of magnetic resonance diffusion spectrum imaging in the nervous system[J]. Chin J Magn Reson Imaging, 2020, 11(9): 809-812, 816. DOI: 10.12015/issn.1674-8034.2020.09.020.
Carvalho J, Invernizzi A, Martins J, et al. Visual field reconstruction using fMRI-based techniques[J/OL]. Transl Vis Sci Technol, 2021, 10(1): 25 [2022-03-24]. DOI: 10.1167/tvst.10.1.25.
Prabhakaran GT, Carvalho J, Invernizzi A, et al. Foveal pRF properties in the visual cortex depend on the extent of stimulated visual field[J/OL]. NeuroImage, 2020, 222: 117250 [2022-03-20]. DOI: 10.1016/j.neuroimage.2020.117250.
Prabhakaran GT, Al-Nosairy KO, Tempelmann C, et al. Mapping visual field defects with fMRI - impact of approach and experimental conditions[J/OL]. Front Neurosci, 2021, 15: 745886 [2022-03-20]. DOI: 10.3389/fnins.2021.745886.
Qing GP, Zhang SD, Wang B, et al. Functional MRI signal changes in primary visual cortex corresponding to the central normal visual field of patients with primary open-angle glaucoma[J]. Invest Ophthalmol Vis Sci, 2010, 51(9): 4627-4634. DOI: 10.1167/iovs.09-4834.
El-Rafei A, Engelhorn T, Wärntges S, et al. Glaucoma classification based on visual pathway analysis using diffusion tensor imaging[J]. Magn Reson Imaging, 2013, 31(7): 1081-1091. DOI: 10.1016/j.mri.2013.01.001.
Zhang P, Wen W, Sun XH, et al. Selective reduction of fMRI responses to transient achromatic stimuli in the magnocellular layers of the LGN and the superficial layer of the SC of early glaucoma patients[J]. Hum Brain Mapp, 2016, 37(2): 558-569. DOI: 10.1002/hbm.23049.
Zhou W, Muir ER, Nagi KS, et al. Retinotopic fMRI reveals visual dysfunction and functional reorganization in the visual cortex of mild to moderate glaucoma patients[J]. J Glaucoma, 2017, 26(5): 430-437. DOI: 10.1097/IJG.0000000000000641.
Borges VM, Danesh-Meyer HV, Black JM, et al. Functional effects of unilateral open-angle glaucoma on the primary and extrastriate visual cortex[J/OL]. J Vis, 2015, 15(15): 9 [2022-03-20]. DOI: 10.1167/15.15.9.
Bolacchi F, Garaci FG, Martucci A, et al. Differences between proximal versus distal intraorbital optic nerve diffusion tensor magnetic resonance imaging properties in glaucoma patients[J]. Invest Ophthalmol Vis Sci, 2012, 53(7): 4191-4196. DOI: 10.1167/iovs.11-9345.
Li T, Liu ZY, Li JH, et al. Altered amplitude of low-frequency fluctuation in primary open-angle glaucoma: a resting-state FMRI study[J]. Invest Ophthalmol Vis Sci, 2014, 56(1): 322-329. DOI: 10.1167/iovs.14-14974.
Li HL, Chou XM, Liang Y, et al. Use of rsfMRI-fALFF for the detection of changes in brain activity in patients with normal-tension glaucoma[J]. Acta Radiol, 2021, 62(3): 414-422. DOI: 10.1177/0284185120926901.
Song YW, Mu KT, Wang JM, et al. Altered spontaneous brain activity in primary open angle glaucoma: a resting-state functional magnetic resonance imaging study[J]. PLoS One, 2014, 9(2): e89493 [2022-03-20]. DOI: 10.1371/journal.pone.0089493.
Dai H, Morelli JN, Ai F, et al. Resting-state functional MRI: functional connectivity analysis of the visual cortex in primary open-angle glaucoma patients[J]. Hum Brain Mapp, 2013, 34(10): 2455-2463. DOI: 10.1002/hbm.22079.
Wang JQ, Li T, Zhou P, et al. Altered functional connectivity within and between the default model network and the visual network in primary open-angle glaucoma: a resting-state fMRI study[J]. Brain Imaging Behav, 2017, 11(4): 1154-1163. DOI: 10.1007/s11682-016-9597-3.
Wang BJ, Yan TQ, Zhou J, et al. Altered fMRI-derived functional connectivity in patients with high-tension glaucoma[J]. J De Neuroradiol, 2021, 48(2): 94-98. DOI: 10.1016/j.neurad.2020.03.001.
Wang Y, Lu WZ, Xie YZ, et al. Functional alterations in resting-state visual networks in high-tension glaucoma: an independent component analysis[J/OL]. Front Hum Neurosci, 2020, 14: 330 [2022-03-20]. DOI: 10.3389/fnhum.2020.00330.
Wang Q, Chen WW, Wang HZ, et al. Reduced functional and anatomic interhemispheric homotopic connectivity in primary open-angle glaucoma: a combined resting state-fMRI and DTI study[J]. Invest Ophthalmol Vis Sci, 2018, 59(5): 1861-1868. DOI: 10.1167/iovs.17-23291.
Wang JQ, Li T, Wang NL, et al. Graph theoretical analysis reveals the reorganization of the brain network pattern in primary open angle glaucoma patients[J]. Eur Radiol, 2016, 26(11): 3957-3967. DOI: 10.1007/s00330-016-4221-x.
Demaria G, Invernizzi A, Ombelet D, et al. Binocular integrated visual field deficits are associated with changes in local network function in primary open-angle glaucoma: a resting-state fMRI study[J/OL]. Front Aging Neurosci, 2022, 13: 744139 [2022-03-24]. DOI: 10.3389/fnagi.2021.744139.
Minosse S, Garaci F, Martucci A, et al. Primary open angle glaucoma is associated with functional brain network reorganization[J/OL]. Front Neurol, 2019, 10: 1134 [2022-03-20]. DOI: 10.3389/fneur.2019.01134.
Qu HY, Wang Y, Yan TQ, et al. Data-driven parcellation approaches based on functional connectivity of visual cortices in primary open-angle glaucoma[J/OL]. Invest Ophthalmol Vis Sci, 2020, 61(8): 33 [2022-03-20]. DOI: 10.1167/iovs.61.8.33.
Haller S, Zaharchuk G, Thomas DL, et al. Arterial spin labeling perfusion of the brain: emerging clinical applications[J]. Radiology, 2016, 281(2): 337-356. DOI: 10.1148/radiol.2016150789.
Wang Q, Chen WW, Qu XX, et al. Reduced cerebral blood flow in the visual cortex and its correlation with glaucomatous structural damage to the retina in patients with mild to moderate primary open-angle glaucoma[J]. J Glaucoma, 2018, 27(9): 816-822. DOI: 10.1097/IJG.0000000000001017.
Zhang SD, Wang B, Xie Y, et al. Retinotopic changes in the gray matter volume and cerebral blood flow in the primary visual cortex of patients with primary open-angle glaucoma[J]. Invest Ophthalmol Vis Sci, 2015, 56(10): 6171-6178. DOI: 10.1167/iovs.15-17286.
Golay X, Ho ML. Multidelay ASL of the pediatric brain[J/OL]. Br J Radiol, 2022, 95(1134): 20220034 [2022-03-24]. DOI: 10.1259/bjr.20220034.
Aksoy DÖ, Umurhan Akkan JC, Alkan A, et al. Magnetic resonance spectroscopy features of the visual pathways in patients with glaucoma[J]. Clin Neuroradiol, 2019, 29(4): 615-621. DOI: 10.1007/s00062-018-0728-7.
Sidek S, Ramli N, Rahmat K, et al. In vivo proton magnetic resonance spectroscopy (1H-MRS) evaluation of the metabolite concentration of optic radiation in primary open angle glaucoma[J]. Eur Radiol, 2016, 26(12): 4404-4412. DOI: 10.1007/s00330-016-4279-5.
Barbosa Breda J, Croitor Sava A, Himmelreich U, et al. Metabolomic profiling of aqueous humor from glaucoma patients-The metabolomics in surgical ophthalmological patients (MISO) study[J/OL]. Exp Eye Res, 2020, 201: 108268 [2022-03-20]. DOI: 10.1016/j.exer.2020.108268.

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